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Molecular and Cellular Biology

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https://www.readbyqxmd.com/read/28416638/eya2-a-target-activated-by-plzf-is-critical-for-plzf-rara-induced-leukemogenesis
#1
Ryoichi Ono, Masahiro Masuya, Satomi Ishii, Naoyuki Katayama, Tetsuya Nosaka
PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416637/a-kinase-independent-role-for-cdk19-in-p53-response
#2
K Audrey Audetat, Matthew D Galbraith, Aaron T Odell, Thomas Lee, Ahwan Pandey, Joaquin M Espinosa, Robin D Dowell, Dylan J Taatjes
The human Mediator complex regulates RNA Polymerase II transcription genome-wide. A general factor that regulates Mediator function is the four-subunit kinase module, which contains either CDK8 or CDK19. Whereas CDK8 is linked to specific signaling cascades and oncogenesis, the cellular roles of its paralog, CDK19, are poorly studied. We discovered that osteosarcoma cells (SJSA) are naturally depleted of CDK8 protein. Whereas stable CDK19 knockdown was tolerated in SJSA cells, proliferation was reduced. Notably, proliferation defects were rescued upon re-expression of wild-type or kinase-dead CDK19...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416636/p53-dynamically-directs-tfiid-assembly-on-target-gene-promoters
#3
R A Coleman, Z Qiao, S K Singh, C S Peng, M Cianfrocco, Z Zhang, A Piasecka, H Aldeborgh, G Basishvili, W L Liu
p53 is a central regulator that turns on vast gene networks to maintain cellular integrity upon various stimuli. p53 activates transcription initiation in part by aiding recruitment of TFIID to the promoter. However, the precise means by which p53 dynamically interacts with TFIID to facilitate assembly on target gene promoters remains elusive. To address this key question, we have undertaken an integrated approach involving single molecule fluorescence microscopy, single particle cryo-electron microscopy, and biochemistry...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416635/vprbp-dcaf1-regulates-the-degradation-and-non-proteolytic-activation-of-the-cell-cycle-transcription-factor-foxm1
#4
Xianxi Wang, Anthony Arceci, Kelly Bird, Christine A Mills, Rajarshi Choudhury, Jennifer L Kernan, Chunxiao Zhou, Victoria Bae-Jump, Albert Bowers, Michael J Emanuele
The oncogenic transcription factor FoxM1 plays a vital role in cell cycle progression, is activated in numerous human malignancies and linked to chromosome instability. We characterize here a Cullin4-based E3 ubiquitin ligase and its substrate receptor VprBP/DCAF1 (CRL4(VprBP)) that we show regulate FoxM1 ubiquitylation and degradation. Paradoxically, we also found that the substrate receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression strongly activates a FoxM1 transcriptional reporter...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416634/a-molecular-mechanism-to-switch-the-aryl-hydrocarbon-receptor-from-a-transcription-factor-to-an-e3-ubiquitin-ligase
#5
Sandra Luecke-Johansson, Michael Gralla, Helene Rundqvist, Jolene Caifeng Ho, Randall S Johnson, Katarina Gradin, Lorenz Poellinger
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is known as a mediator of toxic responses. Recently, it was shown that AhR has dual functions. Besides being a transcription factor it also possesses an intrinsic E3 ubiquitin ligase function that targets e.g. the steroids receptors for proteasomal degradation. The aim of the study was to identify the molecular switch that determines whether AhR acts as a transcription factor or an E3 ubiquitin ligase. To do that, we used the breast cancer cell line MCF7, which expresses a functional ERα signaling pathway...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28396559/an-mrna-capping-enzyme-targets-fact-to-the-active-gene-to-enhance-the-engagement-of-rna-polymerase-ii-into-transcriptional-elongation
#6
Rwik Sen, Amala Kaja, Jannatul Ferdoush, Shweta Lahudkar, Priyanka Barman, Sukesh R Bhaumik
We have recently demonstrated that an mRNA-capping enzyme, Cet1, impairs promoter proximal accumulation/pausing of RNA polymerase II (pol-II) independently of its capping activity in Saccharomyces cerevisiae to control transcription. However, it is yet unknown how pol-II pausing is regulated by Cet1. Here, we show that Cet1's N-terminal domain (NTD) promotes the recruitment of FACT (FAcilitates Chromatin Transcription that enhances engagement of pol-II into transcriptional elongation) to the coding sequence of an active gene, ADH1, independently of mRNA-capping activity...
April 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28373292/caloric-restriction-extends-yeast-chronological-lifespan-by-optimizing-the-snf1-ampk-signaling-pathway
#7
Margaret B Wierman, Nazif Maqani, Erika Strickler, Mingguang Li, Jeffrey S Smith
AMP-activated protein kinase (AMPK) and the homologous yeast SNF1 complex, are key regulators of energy metabolism that counteract nutrient deficiency and ATP depletion by phosphorylating multiple enzymes and transcription factors that maintain energetic homeostasis. AMPK/SNF1 also promotes longevity in several model organisms, including yeast. Here we investigate the role of yeast SNF1 in mediating the extension of chronological lifespan (CLS) by caloric restriction (CR). We find that SNF1 activity is required throughout the log to stationary phase transition (diauxic shift) for effective CLS extension...
April 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28373291/dual-mechanism-of-rag-gene-repression-by-c-myb-during-pre-b-cell-proliferation
#8
Greg A Timblin, Liangqi Xie, Robert Tjian, Mark S Schlissel
Developing B lymphocytes undergo clonal expansion following successful immunoglobulin heavy chain gene rearrangement. During this proliferative burst, expression of the Rag genes is transiently repressed to prevent the generation of dsDNA breaks in cycling large pre-B cells. The Rag genes are then re-expressed in small resting pre-B cells for immunoglobulin light chain gene rearrangement. We previously identified c-Myb as a repressor of Rag transcription during clonal expansion using Abelson murine leukemia virus-transformed B cells...
April 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320876/taking-a-step-back-from-back-translocation-an-integrative-view-of-lepa-ef4-s-cellular-function
#9
Jalyce L E Heller, Rajashekhar Kamalampeta, Hans-Joachim Wieden
Protein synthesis, the translation of mRNA into a polypeptide facilitated by the ribosome, is assisted by a variety of protein factors, some of which are GTPases. In addition to four highly conserved and well-understood GTPases with known function, there are also a number of non-canonical GTPases that are implicated in translation but whose functions are not fully understood. LepA/EF4 is one of these non-canonical GTPases. It is highly conserved and present in bacteria, mitochondria and chloroplasts, but its functional role in the cell remains unknown...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320875/gata3-abundance-is-a-critical-determinant-of-t-cell-receptor-beta-allelic-exclusion
#10
Chia-Jui Ku, JoAnn M Sekiguchi, Bharat Panwar, Yuanfang Guan, Satoru Takahashi, Keigyou Yoh, Ivan Maillard, Tomonori Hosoya, James Douglas Engel
Allelic exclusion describes the essential immunological process by which feedback repression of sequential DNA rearrangements ensures that only one autosome expresses a functional T or B cell receptor. In wild type mammals, approximately 60% of cells have recombined the DNA of one Tcrb V-to-DJ-joined allele in a functional configuration, while the second allele has only recombined the DJ sequences; the other 40% of the cells have recombined the V- to the DJ segments on both alleles, with only one of the two predicting a functional TCRβ protein...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320874/enos-dependent-s-nitrosylation-of-%C3%AE-catenin-prevents-its-association-with-tcf4-and-inhibits-proliferation-of-endothelial-cells-by-wnt3a
#11
Ying Zhang, Rony Chidiac, Chantal Delisle, Jean-Philippe Gratton
Nitric oxide (NO) produced by endothelial NO synthase (eNOS) modulates many functions in endothelial cells. S-nitrosylation (SNO) of cysteine residues on β-catenin by eNOS-derived NO has been shown to influence intercellular contacts between endothelial cells. However, the implication of SNO in the regulation of β-catenin transcriptional activity is ill-defined. Here we report that NO inhibits the transcriptional activity of β-catenin and endothelial cell proliferation induced by activation of Wnt/β-catenin signaling...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320873/sav1-loss-induces-senescence-and-stat3-activation-coinciding-with-tubulointerstitial-fibrosis
#12
Janet Y Leung, Harper L Wilson, Kristin J Voltzke, Lindsay A Williams, Hyo Jin Lee, Sara E Wobker, William Y Kim
Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Here, we show that conditional inactivation of Sav1 in the mouse renal epithelium resulted in upregulated expression of profibrotic genes and TIF. Loss of Sav1 induced Stat3 activation and a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointerstitial fibrosis. Treatment of mice with the YAP inhibitor, Verteporfin (VP), inhibited activation of genes associated with senescence, SASP and activation of Stat3 as well as impeded the development of fibrosis...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320872/the-drosophila-daxx-like-protein-dlp-cooperates-with-asf1-for-h3-3-deposition-and-heterochromatin-formation
#13
Catherine Fromental-Ramain, Philippe Ramain, Ali Hamiche
Histone variants are non-allelic isoforms of canonical histones and they are deposited, in contrast to canonical histones, in a replication-independent (RI) manner. RI deposition of H3.3, a histone variant from the H3.3 family, is mediated in mammals by distinct pathways involving either the histone regulator A (HIRA) complex or the death-associated protein (DAXX)/α-thalassemia X-linked mental retardation protein (ATRX) complex. Here, we investigated the function of Drosophila DAXX Like Protein (DLP) by using both fly genetics approaches and protein biochemistry...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28320871/essential-roles-of-l-type-amino-acid-transporter-1-in-syncytiotrophoblast-development-by-presenting-fusogenic-4f2hc
#14
Ryuichi Ohgaki, Takahiro Ohmori, Saori Hara, Saya Nakagomi, Masami Kanai-Azuma, Kazuko Kaneda-Nakashima, Suguru Okuda, Shushi Nagamori, Yoshikatsu Kanai
Layer(s) of epithelial syncytium, syncytiotrophoblast, differentiates from chorionic trophoblasts via cell fusion and separates maternal and fetal circulations in hemochorial placentas. L-type amino acid transporter 1 (LAT1) and its covalently-linked ancillary subunit 4F2hc are colocalized on both maternal and fetal surface of syncytiotrophoblasts, implying their roles in amino acid transfer through the placental barrier. In this study, LAT1 knockout, in addition, revealed a novel role of LAT1 in syncytiotrophoblast development...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28289076/fumarate-mediates-a-chronic-proliferative-signal-in-fumarate-hydratase-inactivated-cancer-cells-by-increasing-transcription-and-translation-of-ferritin-genes
#15
Michael John Kerins, Ajay Vashisht, Benjamin Xi-Tong Liang, Spencer Jordan Duckworth, Brandon John Praslicka, James Akira Wohlschlegel, Aikseng Ooi
Germline mutations of the gene encoding the tricarboxylic acid cycle (TCA cycle) enzyme, fumarate hydratase (FH), cause a hereditary cancer syndrome known as hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC associated tumors harbor biallelic FH inactivation that results in the accumulation of the TCA cycle metabolite, fumarate. Although it is known that the fumarate accumulation can alter cellular signaling, if and how fumarate confers a growth advantage remains unclear. Here we show that fumarate accumulation confers a chronic proliferative signal by disrupting cellular iron signaling...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28289075/coordinated-hsp110-and-hsp104-activities-power-protein-disaggregation-in-saccharomyces-cerevisiae
#16
Jayasankar Mohanakrishnan Kaimal, Ganapathi Kandasamy, Fabian Gasser, Claes Andréasson
Protein aggregation is intimately associated with cellular stress and is accelerated during aging, disease and cellular dysfunction. Yeast cells rely on the ATP-consuming chaperone Hsp104 to disaggregate proteins together with Hsp70. Hsp110s are ancient and abundant chaperones that form complexes with Hsp70. Here we provide in vivo data showing that yeast Hsp110s Sse1 and Sse2 are essential for Hsp104-dependent protein disaggregation. Following heat shock, complexes of Hsp110 and Hsp70 are recruited to protein aggregates and functions together with Hsp104 in the disaggregation process...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28289074/t-cell-costimulation-by-cd6-is-dependent-on-bivalent-binding-of-a-gads-slp-76-complex
#17
Johannes Breuning, Marion H Brown
The cell surface receptor, CD6 regulates T cell activation in both an activating and inhibitory manner. The adaptor protein SLP-76 is recruited to the CD6 cytoplasmic phosphorylated Y662 residue during T cell activation, providing an activating signal to T cells. In this study, a biochemical approach identified the SH2 domain-containing adaptor protein GADS as the dominant interaction partner for the CD6 cytoplasmic Y629 residue. Functional experiments in human Jurkat and primary T cells showed that mutation of both Y629F and Y662F abolished costimulation by CD6...
March 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28265004/gain-of-function-mutation-of-tristetraprolin-impairs-negative-feedback-control-of-macrophages-in-vitro-yet-has-overwhelmingly-anti-inflammatory-consequences-in-vivo
#18
John D O'Neil, Ewan A Ross, Michael L Ridley, Qize Ding, Tina Tang, Dalya R Rosner, Thomas Crowley, Deepak Malhi, Jonathan L Dean, Tim Smallie, Christopher D Buckley, Andrew R Clark
The mRNA destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3' untranslated regions of many pro-inflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by over-expression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent anti-inflammatory cytokine interleukin 10. Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of pro-inflammatory factors via direct or indirect mechanisms...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28265003/sorla-in-interleukin-6-signaling-and-turnover
#19
Jakob Vejby Larsen, Claus Munck Petersen
Interleukin-6 (IL-6) is a multifunctional cytokine with important functions in various physiologic processes. Mice lacking IL-6 exhibit multiple phenotypic abnormalities such as an inadequate immune and acute-phase response, and elevated levels of circulating IL-6 have been found to accompany several pathologic conditions. IL-6 binds the non-signaling IL-6 receptor (IL-6R) - which is expressed as a transmembrane, as well as a secreted circulating protein - before it engages homodimeric gp130 for signaling. Complex-formation between IL-6 and the membrane-bound IL-6 receptor gives rise to classic cis-signaling, whereas complex-formation between IL-6 and the soluble IL-6R results in trans-signaling...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28265002/deletion-of-pofut1-in-mouse-skeletal-myofibers-induces-muscle-aging-related-phenotypes-in-cis-and-in-trans
#20
Deborah A Zygmunt, Neha Singhal, Mi-Lyang Kim, Megan L Cramer, Kelly E Crowe, Rui Xu, Ying Jia, Jessica Adair, Isabel Martinez-Pena Y Valenzuela, Mohammed Akaaboune, Peter White, Paulus M Janssen, Paul T Martin
Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that Protein O-fucosyltransferase 1 (Pofut1), a gene that encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction...
March 6, 2017: Molecular and Cellular Biology
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